tbuckley/cabot-search huggingface dataset:
Involuntary Displacements—Making a Bad Situation Worse
Authors: Margot Kushel
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Recommending Higher Valent Pneumococcal Conjugate Vaccine for Older Adults—Reply
Authors: Miwako Kobayashi, Tamara Pilishvili, Fernanda C. Lessa
Journal: JAMA Internal Medicine (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression
Authors: Raquel Maeso-Díaz, Kuo Du, Christopher Pan, Cynthia D. Guy, Seh Hoon Oh, Tianyi Chen, Liuyang Wang, Dennis C. Ko, Linda Tang, Rajesh K. Dutta, Ji Hye Jun, Ayako Suzuki, Manal F. Abdelmalek, Xiao-Fan Wang, Anna Mae Diehl
Journal: Hepatology (2023)

Background and Aims: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Senescing cells upregulate thrombomodulin–protease-activated receptor-1 (THBD-PAR1) signaling to remain viable. Vorapaxar blocks the activity of that pathway. We used vorapaxar to determine if and how THBD-PAR1 signaling promotes fibrosis progression in NASH. Approach and Results: We evaluated the THBD-PAR1 pathway in liver biopsies from patients with NAFLD. Chow-fed mice were treated with viral vectors to overexpress p16 in hepatocytes and induce replicative senescence. Effects on the THBD-PAR1 axis and regenerative capacity were assessed; the transcriptome of p16-overexpressing hepatocytes was characterized, and we examined how conditioned medium from senescent but viable (dubbed “undead”) hepatocytes reprograms HSCs. Mouse models of NASH caused by genetic obesity or Western diet/CCl 4 were treated with vorapaxar to determine effects on hepatocyte senescence and liver damage. Inducing senescence upregulates the THBD-PAR1 signaling axis in hepatocytes and induces their expression of fibrogenic factors, including hedgehog ligands. Hepatocyte THBD-PAR1 signaling increases in NAFLD and supports sustained hepatocyte senescence that limits effective liver regeneration and promotes maladaptive repair. Inhibiting PAR1 signaling with vorapaxar interrupts this process, reduces the burden of ‘undead’ senescent cells, and safely improves NASH and fibrosis despite ongoing lipotoxic stress. Conclusion: The THBD-PAR1 signaling axis is a novel therapeutic target for NASH because blocking this pathway prevents accumulation of senescing but viable hepatocytes that generate factors that promote maladaptive liver repair.
Oral administration of PET tracers: Current status
Authors: Giordana Salvi de Souza, Dimitri B.A. Mantovani, Pascalle Mossel, Bartholomeus C.M. Haarman, Ana Maria Marques da Silva, Hendrikus H. Boersma, Cristiane R.G. Furini, Adriaan A. Lammertsma, Charalampos Tsoumpas, Gert Luurtsema
Journal: Journal of Controlled Release (2023)

The oral route is the most widely used and preferable way of drug administration. Several pharmacokinetic processes play a role in the distribution of administered drugs. Therefore, accurate quantification of absorption, distribution, metabolism, excretion, and characterisation of drug kinetics after oral administration is extremely important for developing new human drugs. In vivo methods, such as gamma-scintigraphy, magnetic resonance imaging (MRI), and positron emission tomography (PET), have been used to analyse gastrointestinal tract (GIT) absorption behaviour. This scoping review provides an overview of PET studies that used oral tracer administration. A systematic literature search was performed using PubMed, EMBASE, Scopus, Science Direct, and Web of Science databases. Extensive variation between these studies was seen concerning acquisition protocols, quantification methods, and pharmacokinetic outcome parameters. Studies in humans indicate that it takes 10 to 30 min for the tracer to be in the intestine and about 100 min to reach its maximum concentration in the brain. In rodent studies, different pharmacokinetic parameters for the brain, blood, and GIT were estimated, showing the potential of PET to measure the absorption and distribution of drugs and pharmaceuticals non-invasively. Finally, regarding radiation protection, oral administration has a higher absorbed dose in GIT and, consequently, a higher effective dose. However, with the recent introduction of Long Axial Field of View (LAFOV) PET scanners, it is possible to reduce the administered dose, making oral administration feasible for routine clinical studies.
Enhancing oral delivery of plant-derived vesicles for colitis
Authors: Yuan Liu, Adrian Lankenau Ahumada, Emine Bayraktar, Paul Schwartz, Mamur Chowdhury, Sixiang Shi, Manu M. Sebastian, Htet Khant, Natalia de Val, Nazende Nur Bayram, Guodong Zhang, Thanh Chung Vu, Zuliang Jie, Nicholas B. Jennings, Cristian Rodriguez-Aguayo, Jody Swain, Elaine Stur, Lingegowda S. Mangala, Yutuan Wu, Supriya Nagaraju, Brooke Ermias, Chun Li, Gabriel Lopez-Berestein, Janet Braam, Anil K. Sood
Journal: Journal of Controlled Release (2023)
175 Years of Bilirubin Testing: Ready for Point‐of‐Care?
Authors: Natalie Guirguis, Antoine‐Xavier Bertrand, Christopher F. Rose, Simon Matoori
Journal: Advanced Healthcare Materials (2023)

Abstract Bilirubin was first detected in blood in 1847 and since then has become one of the most widely used biomarkers for liver disease. Clinical routine bilirubin testing is performed at the hospital laboratory, and the gold standard colorimetric test is prone to interferences. The absence of a bedside test for bilirubin delays critical clinical decisions for patients with liver disease. This clinical care gap has motivated the development of a new generation of bioengineered point‐of‐care bilirubin assays. In this Perspective, recently developed bilirubin assays are critically discussed, and their translational potential evaluated.
US Preventive Services Task Force Challenged in Federal Court
Authors: Gregory Curfman, Kirsten Bibbins-Domingo
Journal: JAMA (2023)

For nearly 40 years, the US Preventive Services Task Force (USPSTF) has issued evidence-based recommendations about clinical preventive services in the interest of health promotion and disease prevention for the US. 1 The USPSTF was first convened in 1984 by the US Department of Health and Human Services (HHS), in part to address concerns that few clinicians were focused on interventions related to prevention because of lack of clarity on the evidence base for the effectiveness of these interventions. 2 The USPSTF regularly issues recommendations on a variety of important preventive health services based on an explicit evidence-based approach that includes input from relevant stakeholders and opportunity for public comment.These recommendation statements and the evidence reports on which they are based are posted on the USPSTF website and published in JAMA with commentary in the journals across the JAMA Network and broadly available to clinicians, patients, and the public.Exemplary topics covered by the recommendations range from cancer screening (eg, breast, colon, prostate), screening for osteoporosis, the use of aspirin for the prevention of cardiovascular disease, and preexposure prophylaxis (PrEP) for the prevention of HIV, among many others.In 1999, Congress mandated the director of the Agency for Healthcare Research and Quality (AHRQ), an agency within HHS, to convene and appoint members to the USPSTF and to provide administrative, research, and technical support for its work.Although supported by AHRQ, the work of the USPSTF has always been independent, a feature that has been viewed as critical for supporting the integrity of the scientific process in which it is engaged. 3n 2010, a provision ( §2713) in the Affordable Care Act (ACA) mandated first-dollar insurance coverage by commercial insurers for a range of preventive health services, notably those recommended with an "A" or "B" rating by the USPSTF.The rationale of linking insurance coverage for clinical preventive services to an established, evidence-based process for determining the efficacy of such services seems clear and compelling.Importantly, the ACA coverage linkage did not change the work and processes of the USPSTF, consistent with its independent charge to focus on the science of prevention.The leadership of the USPSTF has often reaffirmed its role as solely focused on evaluation of the science supporting a preventive service, not on determining coverage. 4The actual coverage determination is much more complex and does not involve the USPSTF, although having evidence-based efficacy as one key component in determining coverage seems wise.
Daratumumab for a Patient With Refractory Antineutrophil Cytoplasmatic Antibody–Associated Vasculitis
Authors: Torben M. Rixecker, Philipp M. Lepper, Sebastian Mang, Pascal Espig, Katharina Brill, Lorenz Thurner, Joerg Thomas Bittenbring
Journal: JAMA Internal Medicine (2023)

This case reports on a patient with antineutrophil cytoplasmatic antibody–associated vasculitis and severe pulmonary and cutaneous involvement who received conventional therapy that failed and who was rescued by daratumumab therapy.
Treatment of moderate-to-severe alopecia areata in pre-adolescent children with baricitinib
Authors: Leila Asfour, Laita Bokhari, Bevin Bhoyrul, Samantha Eisman, Anthony Moussa, Huw  Rees, Rodney D Sinclair
Journal: British Journal of Dermatology (2023)

Journal Article Corrected proof Treatment of moderate-to-severe alopecia areata with baricitinib in preadolescent children Get access Leila Asfour, Leila Asfour Sinclair Dermatology Correspondence: Leila Asfour. Email: leila.asfour@srft.nhs.uk https://orcid.org/0000-0002-0049-8377 Search for other works by this author on: Oxford Academic Google Scholar Laita Bokhari, Laita Bokhari Sinclair Dermatology Search for other works by this author on: Oxford Academic Google Scholar Bevin Bhoyrul, Bevin Bhoyrul Sinclair Dermatology Search for other works by this author on: Oxford Academic Google Scholar Samantha Eisman, Samantha Eisman Sinclair Dermatology Search for other works by this author on: Oxford Academic Google Scholar Anthony Moussa, Anthony Moussa Sinclair Dermatology Search for other works by this author on: Oxford Academic Google Scholar Huw Rees, Huw Rees Sinclair Dermatology https://orcid.org/0000-0003-2609-4474 Search for other works by this author on: Oxford Academic Google Scholar Rodney D Sinclair Rodney D Sinclair Sinclair DermatologyUniversity of Melbourne, Melbourne, Australia Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad118, https://doi.org/10.1093/bjd/ljad118 Published: 10 April 2023 Article history Received: 09 August 2022 Revision received: 02 April 2023 Accepted: 04 April 2023 Published: 10 April 2023 Corrected and typeset: 19 June 2023
Racial and Ethnic Disparities in Health Care Use and Access Associated With Loss of Medicaid Supplemental Insurance Eligibility Above the Federal Poverty Level
Authors: Eric T. Roberts, Youngmin Kwon, Alexandra G. Hames, J. Michael McWilliams, John Z. Ayanian, Renuka Tipirneni
Journal: JAMA Internal Medicine (2023)

Medicaid supplemental insurance covers most cost sharing in Medicare. Among low-income Medicare beneficiaries, the loss of Medicaid eligibility above this program's income eligibility threshold (100% of federal poverty level [FPL]) may exacerbate racial and ethnic disparities in Medicare beneficiaries' ability to afford care.
Cost-Free Preventive Care Under the ACA Faces Legal Challenge
Authors: Abbe R. Gluck, Lawrence O. Gostin
Journal: JAMA (2023)

This Viewpoint examines the recent decision by a federal district court that undercuts the Affordable Care Act’s mandate for cost-free coverage of preventive services, including contraception, some vaccinations, many screenings, and preexposure prophylaxis for HIV, among others.
Letter to the Editor: Progressive cholestasis and associated sclerosing cholangitis are complications of COVID-19 in patients with chronic liver disease
Authors: Sumayya Umar, Arsalan Nadeem, Muntaha Nadeem
Journal: Hepatology (2023)

To the editor, We read the article by Hartl et al1 with great intrigue. The study concluded that 20% of patients with chronic liver disease (CLD) develop progressive cholestasis after severe acute respiratory syndrome coronavirus-2 infection and patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or secondary sclerosing cholangitis after COVID-19. Although this study adds to the growing evidence that CLD patients are likely to have higher mortality rates due to severe acute respiratory syndrome coronavirus-2 infection, several points are worthy of mention. First, in this study, stratification was done according to the severity of CLD. We think that an additional stratification according to the etiology of liver disease is warranted, as many studies have demonstrated that etiology is an independent risk factor for adverse clinical outcomes. Two reviews published in 2023 describe the role of etiology in the morbidity of severe acute respiratory syndrome coronavirus-2 infection. They conclude that COVID-19 infection in alcohol-associated liver disease and NAFLD patients are most frequently associated with adverse outcomes, whereas other etiologies such as chronic viral hepatitis due to HBV do not seem to affect the prognosis of COVID-19 infection.2,3 Second, this study included only hospitalized patients, which can increase bias. Antiviral drugs, antibiotics, and corticosteroids are all used to treat hospitalized COVID-19 patients and are known to cause liver injury. The reported incidence of DILI in patients with COVID-19 is 25.4%.4 Additional analysis should have been done to control for potential confounders to strengthen the evidence. Third, this study included hospitalized COVID-19 patients between March 2020 and July 2021. Although the COVID-19 vaccine became globally available in late 2020, the vaccination status of the patients included in the study is not specified. Vaccination has resulted in decreased hospitalization and mortality rates in CLD patients. However, CLD patients are underrepresented in vaccine trials, and additional studies on their efficacy and safety in these patients need to be done.2 This study failed to provide any evidence about either the benefits or the risks in CLD patients.
Reply: NAFLD/MAFLD: One size does not fit all, certainly not for children!
Authors: Linda Henry, Zobair M. Younossi
Journal: Hepatology (2023)

We appreciate the comments by Drs. Hegarty and Dhawan about our recent article on MAFLD and NAFLD.1 Since our publication, the debate about NAFLD and MAFLD has moved into a multi-society consensus assessment that includes adult and pediatric hepatologists from across the world. As the authors correctly pointed out the flaws of NAFLD nomenclature for children, they are also certainly aware of the flaws of using the MAFLD nomenclature in children in which metabolic liver disease among children has little to do with the current definition of MAFLD.2,3 The points raised in our article, those by van Kleef and de Knegt and Hegarty and Dhawan1,2,4 go to the heart of the current debate on what is the most appropriate, non-stigmatizing name for this chronic liver disease.5 We have advocated for changing the name through a careful process that could advance the field without potentially damaging decades of work that has generated evidence about the epidemiology, pathogenesis, biomarker development, and drug development for this fatty liver disease. A change in terminology must also proceed, acknowledging the disease awareness challenges we face in primary care and diabetology practices.6 If the process leads to changing the name of NAFLD to Fatty Liver Disease, this name change could be quite appealing to children. We would urge all our colleagues to contribute and actively engage in the consensus development process. It is only through active participation in the process that we can move the field beyond constant debates to a consensus nomenclature accepted by the majority. We can then generate new work, which will provide evidence about the impact of the new term on the field while continuing to move the field forward.7
Changes in Children’s Recreational Screen Time During the COVID-19 Pandemic
Authors: André Plamondon, Brae Anne McArthur, Rachel Eirich, Nicole Racine, Sheila McDonald, Suzanne Tough, Sheri Madigan
Journal: JAMA Pediatrics (2023)

This cohort study compared children’s recreational screen time with screen time before the COVID-19 pandemic and during 3 pandemic waves to examine whether changes in screen time were greater than those associated with age.
Severe Hippocampal Atrophy in a Patient With Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy
Authors: Frederik Bartels, Josephine Heine, Carsten Finke
Journal: JAMA Neurology (2023)

This case report describes a patient who presented with headache, fever, quadriparesis, and reduced visual acuity in the left eye and 6 months later presented with persistent quadriparesis and new-onset cognitive deficits.
Reply: Progressive cholestasis and associated sclerosing cholangitis are complications of COVID-19 in patients with chronic liver disease
Authors: Lukas Hartl, Thomas Reiberger, Michael Trauner
Journal: Hepatology (2023)

We thank Umar et al1 for their interest in our study.2 Overall NAFLD seems to be associated with impaired COVID-19 outcomes although related studies did not consistently identify NAFLD as an independent risk factor for poor outcomes after severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection.3 In our study, patients with NAFLD were at high risk for developing progressive cholestasis and SSC. In fact, 70% of the patients with SSC had NAFLD as chronic liver disease (CLD) etiology, and most also had obesity, diabetes mellitus, or arterial hypertension—factors that are linked to NAFLD and increased risk for severe COVID-19.3 Importantly, our study only included hospitalized patients with COVID-19. This implies that our results on progressive cholestasis and bile duct injury only apply to hospitalized patients with CLD and COVID-19. However, SSC almost exclusively develops after critical illness,4 so it is unlikely that patients with CLD and COVID-19 without hospitalization and, thus, with mild courses of the disease would develop SSC without being referred to a clinic. DILI is certainly relevant, especially in severe COVID-19. The potential pathogenic role of ketamine should be mentioned in this context,3 as 90% (n = 9/10) of patients developing SSC in our study were exposed to ketamine. Regarding vaccination status, 90% of patients developing SSC in our study were unvaccinated before the SARS-CoV-2 infection. One patient with NAFLD was vaccinated twice with the BNT162b2 vaccine with the second dose being administered ~2 months before the infection. Interestingly, this patient was infected with the delta variant of the virus. Although data on the immunological response to the vaccination in this patient are not available, exposure to at least 2 SARS-CoV-2 vaccination doses usually prevents severe COVID-19 courses in patients with CLD.3 Ultimately, awareness for hepatic and biliary complications of COVID-19—not only in patients with CLD—should remain high, since early and targeted therapy, as modulation of farnesoid-X receptor and angiotensin-converting enzyme-2 signaling,5 may prevent complications and avoid liver transplantation in some cases.
Frequent Overexpression of HER3 in Brain Metastases from Breast and Lung Cancer
Authors: Erwin Tomasich, Ariane Steindl, Christina Paiato, Teresa Hatziioannou, Markus Kleinberger, Luzia Berchtold, Rainer Puhr, Johannes A. Hainfellner, Leonhard Müllauer, Georg Widhalm, Franziska Eckert, Rupert Bartsch, Gerwin Heller, Matthias Preusser, Anna Sophie Berghoff
Journal: Clinical Cancer Research (2023)

Abstract Purpose: HER3 belongs to a family of receptor tyrosine kinases with oncogenic properties and is targeted by a variety of novel anticancer agents. There is a huge unmet medical need for systemic treatment options in patients with brain metastases (BM). Therefore, we aimed to investigate HER3 expression in BM of breast (BCa) and non–small cell lung cancer (NSCLC) as the basis for future clinical trial design. Experimental Design: We analyzed 180 BM samples of breast cancer or NSCLC and 47 corresponding NSCLC extracranial tissue. IHC was performed to evaluate protein expression of HER3, and immune cells based on CD3, CD8, and CD68. To identify dysregulated pathways based on differential DNA methylation patterns, we used Infinium MethylationEPIC microarrays. Results: A total of 99/132 (75.0%) of BCa-BM and 35/48 (72.9%) of NSCLC-BM presented with HER3 expression. Among breast cancer, HER2-positive and HER2-low BM showed significantly higher rates of HER3 coexpression than HER2-negative BM (87.1%/85.7% vs. 61.0%, P = 0.004). Among NSCLC, HER3 was more abundantly expressed in BM than in matched extracranial samples (72.9% vs. 41.3%, P = 0.003). No correlation of HER3 expression and intratumoral immune cell density was observed. HER3 expression did not correlate with overall survival from BM diagnosis. Methylation signatures differed according to HER3 status in BCa-BM samples. Pathway analysis revealed subtype-specific differences, such as TrkB and Wnt signaling pathways dysregulated in HER2-positive and triple-negative breast cancer BM, respectively. Conclusions: HER3 is highly abundant in BM of breast cancer and NSCLC. Given the promising results of antibody–drug conjugates in extracranial disease, BM-specific trials that target HER3 are warranted. See related commentary by Kabraji and Lin, p. 2961